The "protein-only" hypothesis of prion diseases views the infectious agent as devoid of nucleic acids and consisting of misfolded prion proteins (PrP(Sc)) which, upon infiltration into host cells, act as a template that induces transformation of wild-type protein (PrP(C)) to the pathological form by unknown mechanisms. The two isoforms are identical in amino-acid composition. By analogy to reported "silent" mutations in which utilization of relatively rare tRNAs alter protein folding pattern, we postulate that misfolded PrP(Sc) alters tRNAs abundance in prion-infected cells and results in different rates of co-translational folding of PrP, leading to the formation of additional misfolded PrP(Sc). We analyze experiments that might link tRNAs to prions. This concept of "PrP-seed and tRNA-soil" envisages a vicious cycle in which PrP(Sc) levels govern specific tRNA usage, whose alteration subsequently transforms resident PrP(C) to PrP(Sc), causing the cycle to repeat itself ad infinitum.